Nirogacestat, a γ-Secretase Inhibitor for Desmoid Tumors.

BACKGROUND: Desmoid tumors are rare, locally aggressive, highly recurrent soft-tissue tumors without approved treatments. METHODS: We conducted a phase 3, international, double-blind, randomized, placebo-controlled trial of nirogacestat in adults with progressing desmoid tumors according to the Response Evaluation Criteria in Solid Tumors, version 1.1. Patients were assigned in a 1:1 ratio to receive the oral γ-secretase inhibitor nirogacestat (150 mg) or placebo twice daily. The primary end point was progression-free survival. RESULTS: From May 2019 through August 2020, a total of 70 patients were assigned to receive nirogacestat and 72 to receive placebo. Nirogacestat had a significant progression-free survival benefit over placebo (hazard ratio for disease progression or death, 0.29; 95% confidence interval, 0.15 to 0.55; P<0.001); the likelihood of being event-free at 2 years was 76% with nirogacestat and 44% with placebo. Between-group differences in progression-free survival were consistent across prespecified subgroups. The percentage of patients who had an objective response was significantly higher with nirogacestat than with placebo (41% vs. 8%; P<0.001), with a median time to response of 5.6 months and 11.1 months, respectively; the percentage of patients with a complete response was 7% and 0%, respectively. Significant between-group differences in secondary patient-reported outcomes, including pain, symptom burden, physical or role functioning, and health-related quality of life, were observed (P≤0.01). Frequent adverse events with nirogacestat included diarrhea (in 84% of the patients), nausea (in 54%), fatigue (in 51%), hypophosphatemia (in 42%), and maculopapular rash (in 32%); 95% of adverse events were of grade 1 or 2. Among women of childbearing potential receiving nirogacestat, 27 of 36 (75%) had adverse events consistent with ovarian dysfunction, which resolved in 20 women (74%). CONCLUSIONS: Nirogacestat was associated with significant benefits with respect to progression-free survival, objective response, pain, symptom burden, physical functioning, role functioning, and health-related quality of life in adults with progressing desmoid tumors. Adverse events with nirogacestat were frequent but mostly low grade. (Funded by SpringWorks Therapeutics; DeFi ClinicalTrials.gov number, NCT03785964.).

Spotting disease disrupts the microbiome of infected purple sea urchins, Strongylocentrotus purpuratus.

BACKGROUND: Spotting disease infects a variety of sea urchin species across many different marine locations. The disease is characterized by discrete lesions on the body surface composed of discolored necrotic tissue that cause the loss of all surface appendages within the lesioned area. A similar, but separate disease of sea urchins called bald sea urchin disease (BSUD) has overlapping symptoms with spotting disease, resulting in confusions in distinguishing the two diseases. Previous studies have focus on identifying the underlying causative agent of spotting disease, which has resulted in the identification of a wide array of pathogenic bacteria that vary based on location and sea urchin species. Our aim was to investigate the spotting disease infection by characterizing the microbiomes of the animal surface and various tissues. RESULTS: We collected samples of the global body surface, the lesion surface, lesioned and non-lesioned body wall, and coelomic fluid, in addition to samples from healthy sea urchins. 16S rRNA gene was amplified and sequenced from the genomic DNA. Results show that the lesions are composed mainly of Cyclobacteriaceae, Cryomorphaceae, and a few other taxa, and that the microbial composition of lesions is the same for all infected sea urchins. Spotting disease also alters the microbial composition of the non-lesioned body wall and coelomic fluid of infected sea urchins. In our closed aquarium systems, sea urchins contracted spotting disease and BSUD separately and therefore direct comparisons could be made between the microbiomes from diseased and healthy sea urchins. CONCLUSION: Results show that spotting disease and BSUD are separate diseases with distinct symptoms and distinct microbial compositions.

A novel combined approach to placement of a double lumen endobronchial tube using a video laryngoscope and fiberoptic bronchoscope: a retrospective chart review.

BACKGROUND: The objective of this study was to evaluate a modern combined video laryngoscopy and flexible fiberoptic bronchoscope approach to placement of a double lumen endobronchial tube and further characterize potential strengths and weaknesses of this approach. METHODS: Retrospective chart review was conducted at our single institution, academic medical center, tertiary-care hospital. Patients aged 18 years of age or older were evaluated who underwent thoracic surgery and one-lung ventilation with placement of a double lumen endobronchial tube using a novel combined video laryngoscopy and flexible fiberoptic bronchoscope approach. No interventions were performed. RESULTS: Demographics and induction and intubation documentation were reviewed for 21 patients who underwent thoracic surgery and one-lung ventilation with placement of a double lumen endobronchial tube using a novel combined video laryngoscopy and flexible fiberoptic bronchoscope approach. First pass success using the combined approach was 86% (18/21). The five patients with an anticipated difficult airway had successful double lumen endobronchial tube placement on the first attempt. There were no instances of desaturation during double lumen endobronchial tube placement. No airway complications related to double lumen endobronchial tube placement were recorded. CONCLUSION: Use of a combined approach employing video laryngoscopy and a flexible fiberoptic bronchoscope may represent a reliable alternative approach to placement of double lumen endobronchial tubes.

GOunder/Desmoid Tumor Research Foundation DEsmoid Symptom/Impact Scale (GODDESS©): psychometric properties and clinically meaningful thresholds as assessed in the Phase 3 DeFi randomized controlled clinical trial.

PURPOSE: The GODDESS© tool was developed to assess Desmoid Tumor/Aggressive Fibromatosis (DT/AF) symptom severity and impact on patients' lives. This study evaluated GODDESS©'s cross-sectional and longitudinal measurement properties. METHODS: The Phase 3, randomized placebo-controlled, DeFi study (NCT03785964) of nirogacestat in DT/AF was used to assess GODDESS©'s reliability, construct validity, responsiveness, and estimate of meaningful change thresholds (MCTs). Other patient-reported outcome (PRO) measures included Patient Global Impression of Severity (PGIS) in DT/AF symptoms, EORTC QLQ-C30, Brief Pain Inventory Short Form, and PROMIS Physical Function short-form 10a v2.0 plus 3 items. RESULTS: DeFi participants (N = 142) had a median age of 34 years (range: 18-76) and were mostly female (64.8%), with extra-abdominal (76.8%) or intra-abdominal tumors (23.2%). The GODDESS© symptom/impact scales showed internal consistency at baseline, cycles 4 and 7 (Cronbach's α > 0.70) and test-retest reliability (intra-class correlation coefficient > 0.85). GODDESS© scales correlated moderately to highly with PRO measures capturing similar content and differentiated among PGIS and Eastern Cooperative Oncology Group groups. GODDESS© scales detected improvement over time. For the total symptom score, a 1.30-point decrease was estimated as the within-person MCT and a 1.00-point decrease as the between-group MCT. For the physical functioning impact score, estimated within- and between-group MCTs were 0.60-point and 0.50-point decreases, respectively. Few participants exhibited symptom worsening. CONCLUSION: GODDESS© was found to be reliable, valid, responsive, and interpretable as a clinical trial endpoint in the pooled sample of DT/AF patients. Estimated MCTs can be used to define responders and assess group-level differences in future, unblinded, efficacy analyses. TRIAL REGISTRATION NUMBER AND REGISTRATION DATE: NCT03785964; December 24, 2018.

Reciprocity in the intercultural conference space to improve Aboriginal oral health: A qualitative study.

OBJECTIVES: Despite high rates of oral disease in Indigenous communities globally, progress is slow in implementing policies and practices so the depth of inequity is addressed and oral health outcomes improve. Indigenous communities are often poorly consulted in the process. This paper responds to this inequity by seeking to create a respectful intercultural space at international dental conferences where Aboriginal health practitioners and dental public health researchers can discuss ways forward for oral health in Indigenous communities. METHODS: Participatory action research informed by Indigenist methodologies guided this research. Two roundtable discussions between Australian Aboriginal and non-Aboriginal participants were recorded, transcribed and analysed for themes related to problems and potential solutions to dental disease in Indigenous communities. Follow-up discussions on participants' reflections engaging in this intercultural space were recorded and analysed. RESULTS: Two Aboriginal health practitioners and five non-Aboriginal international dental public health researchers identified the importance of inclusion where intercultural engagement and collaboration with Indigenous Peoples were integral to conducting research in this context and improving oral health outcomes. CONCLUSIONS: Creating a safe, respectful space between Aboriginal health practitioners and non-Aboriginal dental public health researchers at an international conference fostered dialogue to better understand barriers and enablers to good oral health outcomes. Intercultural engagement and discussion is a step towards mutual understanding of oral health perspectives and experiences that can foster equity and enable more collaborative responses to improve oral health outcomes.

Prevalence of Acinetobacter baumannii and Candida auris in Patients Receiving Mechanical Ventilation.

Importance: To date, only 1 statewide prevalence survey has been performed for Acinetobacter baumannii (2009) in the US, and no statewide prevalence survey has been performed for Candida auris, making the current burden of these emerging pathogens unknown. Objective: To determine the prevalence of A baumannii and C auris among patients receiving mechanical ventilation in Maryland. Design, Setting, and Participants: The Maryland Multi-Drug Resistant Organism Prevention Collaborative performed a statewide cross-sectional point prevalence of patients receiving mechanical ventilation admitted to acute care hospitals (n = 33) and long-term care facilities (n = 18) between March 7, 2023, and June 8, 2023. Surveillance cultures (sputum, perianal, arm/leg, and axilla/groin) were obtained from all patients receiving mechanical ventilation. Sputum, perianal, and arm/leg cultures were tested for A baumannii and antibiotic susceptibility testing was performed. Axilla/groin cultures were tested by polymerase chain reaction for C auris. Main Outcomes and Measures: Prevalence of A baumannii, carbapenem-resistant A baumannii (CRAB), and C auris. Prevalence was stratified by type of facility. Results: All 51 eligible health care facilities (100%) participated in the survey. A total of 482 patients receiving mechanical ventilation were screened for A baumannii and 470 were screened for C auris. Among the 482 patients who had samples collected, 30.7% (148/482) grew A baumannii, 88 of the 148 (59.5%) of these A baumannii were CRAB, and C auris was identified in 31 of 470 (6.6%). Patients in long-term care facilities were more likely to be colonized with A baumannii (relative risk [RR], 7.66 [95% CI, 5.11-11.50], P < .001), CRAB (RR, 5.48 [95% CI, 3.38-8.91], P < .001), and C auris (RR, 1.97 [95% CI, 0.99-3.92], P = .05) compared with patients in acute care hospitals. Nine patients (29.0%) with cultures positive for C auris were previously unreported to the Maryland Department of Health. Conclusions: A baumannii, carbapenem-resistant A baumannii, and C auris were common among patients receiving mechanical ventilation in both acute care hospitals and long-term care facilities. Both pathogens were significantly more common in long-term care facilities than in acute care hospitals. Patients receiving mechanical ventilation in long-term care facilities are a high-risk population for emerging pathogens, and surveillance and prevention efforts should be targeted to these facilities.

Fuel reduction burning reduces wildfire severity during extreme fire events in south-eastern Australia.

Extreme fire events have increased across south-eastern Australia owing to warmer and drier conditions driven by anthropogenic climate change. Fuel reduction burning is widely applied to reduce the occurrence and severity of wildfires; however, targeted assessment of the effectiveness of this practice is limited, especially under extreme climatic conditions. Our study utilises fire severity atlases for fuel reduction burns and wildfires to examine: (i) patterns in the extent of fuel treatment within planned burns (i.e., burn coverage) across different fire management zones, and; (ii) the effect of fuel reduction burning on the severity of wildfires under extreme climatic conditions. We assessed the effect of fuel reduction burning on wildfire severity across temporal and spatial scales (i.e., point and local landscape), while accounting for burn coverage and fire weather. Fuel reduction burn coverage was substantially lower (∼20-30%) than desired targets in fuel management zones focused on asset protection, but within the desired range in zones that focus on ecological objectives. At the point scale, wildfire severity was moderated in treated areas for at least 2-3 years after fuel treatment in shrubland and 3-5 years in forests, relative to areas that did not receive fuel reduction treatments (i.e., unburnt patches). Fuel availability strongly limited fire occurrence and severity within the first 18 months of fuel reduction burning, irrespective of fire weather. Fire weather was the dominant driver of high severity canopy defoliating fire by ∼3-5 years after fuel treatment. At the local landscape scale (i.e., 250 ha), the extent of high canopy scorch decreased marginally as the extent of recently (<5 years) treated fuels increased, though there was a high level of uncertainty around the effect of recent fuel treatment. Our findings demonstrate that during extreme fire events, very recent (i.e., <3 years) fuel reduction burning can aid wildfire suppression locally (i.e., near assets) but will have a highly variable effect on the extent and severity of wildfires at larger scales. The patchy coverage of fuel reduction burns in the wildland-urban interface indicates that considerable residual fuel hazard will often be present within the bounds of fuel reduction burns.

[Research updates on a role for retinal contrast in myopia control].

Animal research has established that signals derived from both contrast and defocus can influence refractive development, likely concurrently, so that overall refractive development reflects an integration of these primary visual signals. Important findings include the association of L/M opsin mutations with familial high myopia, axial hyperopia produced in response to form deprivation in moderate outdoor lighting levels, effective control of myopia by diffusion optics technology spectacle lenses designed to reduce retinal contrast, and all current defocus-based optical treatments which inadvertently reduce image contrast. In this review, clinical trial results of optical myopia treatment strategies that manipulate retinal contrast are considered in context of animal research outcomes. In conclusion, research suggests mild reductions in retinal contrast can slow myopia progression in children and may also have a role in defocus-based optical therapy.

Examining HIV Stigma, Depression, Stress, and Recent Stimulant Use in a Sample of Sexual Minority Men Living with HIV: An Application of the Stigma and Substance Use Process Model.

Sexual minority men (SMM) with HIV are disproportionately impacted by stigma and mental health disorders. Guided by the Stigma and Substance Use Process Model, we evaluated how HIV stigma impacts mental health outcomes among SMM with HIV. Data were drawn from Thrive With Me, an RCT of an mHealth intervention targeting ART adherence among SMM with HIV. Path analyses tested the relationships between HIV stigma, depression, stress, and recent stimulant use. Overall, 49.1% (194/401) had depression symptoms, 68.8% (276/401) had moderate-to-high stress, and 28.1% (111/401) had detectable stimulant use in urine samples at baseline. In path analyses, baseline internalized HIV stigma was associated with depression and stress 5-months post-baseline and enacted stigma was associated with recent stimulant use 11-months post-baseline. We identified internalized and enacted HIV stigma, but not anticipated stigma, as potentially important intervention targets for stimulant use, depression, and stress among SMM with HIV.

Social environmental impact of COVID-19 and erectile dysfunction: an explorative review.

BACKGROUND: To date, no attempt has been made to collate literature on the relationship between the social environmental impact of COVID-19 and erectile dysfunction. The aim of this explorative review was to assess and compare the prevalence of erectile dysfunction (ED) in male healthcare workers and males during the COVID-19 pandemic. METHODS: A systematic review of major databases from inception to February 2021 was conducted. Prevalence data were extracted, and a random-effects meta-analysis was undertaken. OUTCOMES: The pooled prevalence of ED amongst healthcare workers working in COVID-19 specific environments, and non-healthcare during the COVID-19 pandemic. RESULTS: Of 52 initial studies, six were included for the final analysis. The pooled prevalence of ED in healthcare workers working in a COVID-19 environment was 63.6% (95% CI 20.3-92.3%), and in non-healthcare workers during the COVID-19 pandemic was 31.9% (95% CI 19.5-47.6%). CONCLUSION: The prevalence of ED in healthcare workers working in COVID-19 environments was higher than representative samples and is of concern. Sexual health (and by extension, overall health), should be a priority when considering ways to care for this population. Considering the social environmental impact of COVID-19 on sexual health and in particular on ED, it is important to provide adequate psychological support systems and to promote quality of life with particular attention to sexual health.

Residual neuromuscular blockade in the ICU: a prospective observational study and national survey.

Residual neuromuscular blockade is associated with significant morbidity. It has been widely studied in anaesthesia; however, the incidence of residual neuromuscular blockade in patients managed in the ICU is unknown. We conducted a prospective observational study in a tertiary ICU to determine the incidence of residual neuromuscular blockade using quantitative accelerographic monitoring. We tested for residual neuromuscular blockade (defined as a train-of-four ratio < 0.9) before cessation of sedation in anticipation of tracheal extubation. We also surveyed 16 other ICUs in New Zealand to determine their use of neuromuscular monitoring. A total of 191 patients were included in the final analysis. The incidence (95%CI) of residual neuromuscular blockade was 43% (36-50%), with a similar incidence observed in non-postoperative and postoperative patients. There was a lower risk of residual neuromuscular blockade with atracurium than rocuronium (risk ratio (95%CI) of 0.39 (0.12-0.78)) and a higher risk with pancuronium than rocuronium (1.59 (1.06-2.49)). Our survey shows that, in New Zealand ICUs, monitoring of neuromuscular function is rarely carried out before tracheal extubation. When neuromuscular monitoring is undertaken, it is based on individual clinician suspicion and performed using qualitative measurements. No ICU reported using a quantitative monitor or a clinical guideline. The results demonstrate a high incidence of residual neuromuscular blockade in our ICU patients and identify the type of neuromuscular blocking drug as a possible risk factor. Monitoring neuromuscular function before tracheal extubation is not currently the standard of care in New Zealand ICUs. These data suggest that residual neuromuscular blockade may be an under-recognised problem in ICU practice.

Survival of Clostridioides difficile spores in thermal and chemo-thermal laundering processes and influence of the exosporium on their adherence to cotton bed sheets.

Clostridioides difficile spores were previously demonstrated to survive industrial laundering. Understanding interactions between heat, disinfectants and soiling (e.g. bodily fluids) affecting C. difficile spore survival could inform the optimization of healthcare laundry processes. Reducing spore attachment to linen could also enhance laundering efficacy. This study aimed to compare the sensitivity of C. difficile spores to heat and detergent, with and without soiling and to investigate adherence to cotton. Survival of C. difficile spores exposed to industrial laundering temperatures (71-90°C), reference detergent and industrial detergent was quantified with and without soiling. The adherence to cotton after 0 and 24 h air drying was determined with the exosporium of C. difficile spores partially or fully removed. Clostridioides difficile spores were stable at 71°C for 20 min (≤0·37 log10 reduction) while 90°C was sporicidal (3 log10 reduction); soiling exerted a protective effect. Industrial detergent was more effective at 71°C compared to 25°C (2·81 vs 0·84 log10 reductions), however, specifications for sporicidal activity (>3 log10 reduction) were not met. Clostridioides difficile spores increasingly adhered to cotton over time, with 49% adherence after 24 h. Removal of the exosporium increased adherence by 19-23% compared to untreated spores. Further understanding of the role of the exosporium in attachment to cotton could enhance spore removal and aid decontamination of linen.

Issues and gaps in international guidance and national regulatory systems affecting international live insect trade.

International trade in live insects involves the shipping of many different species, for various purposes, with a variety of handling requirements regulated by numerous authorities with varying objectives. The diversity of factors at play has both created and been subject to a complex regulatory landscape. A review of global production, shipping and use experiences from a range of perspectives has shown gaps and inconsistencies in international guidance and national implementation. Private carriers add another layer of uncertainty that is disproportionate to risks, resulting in variable practices and charges. Many benefits can come from international trade in insects, including pollinator services, control of pests and of disease vectors, and enhanced international scientific research and innovation. These benefits will be better achieved through a more evidence-based and efficient approach to regulating trade. This change in approach will in turn require an improved and widely accepted risk-management landscape for insect trade.

Le commerce international d'insectes vivants s'appuie sur les expéditions de nombreuses espèces différentes à diverses fins, assorties de multiples exigences relatives à la manutention régies par des autorités différentes poursuivant des objectifs distincts. La diversité des facteurs en jeu a rendu nécessaire la création d'un paysage normatif complexe, avec les contraintes qui lui sont associées. L'examen à l'échelle mondiale de la production, du transport et des expériences dans ce domaine depuis diverses perspectives a révélé un certain nombre de lacunes et d'incohérences au niveau des directives internationales et de leurs applications concrètes dans les pays. Les transporteurs privés ajoutent une dimension d'incertitude supplémentaire qui est disproportionnée par rapport aux risques, ce qui entraîne une forte variabilité des pratiques et des charges. Les échanges internationaux d'insectes génèrent nombre d'activités bénéfiques, parmi lesquelles les services de pollinisation, la lutte contre les ravageurs et les vecteurs de maladie, et l'accroissement de la recherche scientifique internationale et de l'innovation. Les objectifs attendus seront mieux atteints en adoptant une approche de la réglementation des échanges qui s'appuie davantage sur des éléments factuels et sur les gains d'efficacité. Ce changement méthodologique nécessitera à son tour la mise en place d'un cadre amélioré et plus largement accepté de la gestion des risques dans le domaine du commerce des insectes.

El comercio internacional de insectos vivos, que supone el transporte de muchas especies diferentes con fines diversos, se acompaña de requisitos de manipulación que dictan numerosas autoridades con todo tipo de objetivos. La diversidad de los factores que entran en juego ha sido a la vez causa y consecuencia de un complejo panorama reglamentario. Los autores, tras describir un estudio a escala mundial de la experiencia de producción, transporte y utilización de insectos vivos desde diferentes puntos de vista, exponen las carencias e incoherencias observadas en las directrices internacionales y su traslación a escala nacional. Los transportistas privados añaden otro factor de incertidumbre que tiene un peso desproporcionado en relación con el nivel de riesgo y se traduce en procedimientos y precios heterogéneos. El comercio internacional de insectos puede traer consigo muchos beneficios, en particular servicios de polinización, control de plagas y de vectores de enfermedad, y avances de la investigación e innovación científica a escala internacional. Pero obtener esos beneficios será más fácil si se aborda la regulación del comercio de manera más eficaz y científicamente fundamentada, operando un cambio de lógica que exigirá, a su vez, la aplicación al comercio de insectos de un régimen más sofisticado y ampliamente aceptado de gestión de los riesgos.

COVID-19 survey burden for health care workers: literature review and audit.

OBJECTIVES: Concerns have been raised about the quantity and quality of research conducted during the COVID-19 pandemic, particularly related to the mental health and wellbeing of health care workers (HCWs). For understanding the volume, source, methodological rigour and degree of overlap in COVID-19, studies were conducted among HCWs in the United Kingdom (UK). STUDY DESIGN: Mixed methods approach, literature review and audit. METHODS: First, a literature review of published research studies and second, an audit of studies HCWs have been invited to complete. For the literature review, we searched Medline, PsycINFO and Nexis, webpages of three medical organisations (Royal Society of Medicine, Royal College of Nursing and British Medical Association), and the YouGov website. For the audit, a non-random purposive sample of six HCWs from different London NHS Trusts reviewed email, WhatsApp and SMS messages they received for study invitations. RESULTS: The literature review identified 27 studies; the audit identified 70 study invitations. Studies identified by the literature review were largely of poor methodological rigour: only eight studies (30%) provided response rate, one study (4%) reported having ethical approval, and one study (4%) reported funding details. There was substantial overlap in the topics measured. In the audit, volunteers received a median of 12 invitations. The largest number of study invitations were for national surveys (n = 23), followed by local surveys (n = 16) and research surveys (n = 8). CONCLUSION: HCWs have been asked to complete numerous surveys that frequently have methodological shortcomings and overlapping aims. Many studies do not follow scientific good-practice and generate questionable, non-generalisable results.

Tiered restrictions for COVID-19 in England: knowledge, motivation and self-reported behaviour.

OBJECTIVES: To test whether public knowledge and confidence in one's understanding of the local restrictions, motivation to adhere to local restrictions, and self-reported behaviour (going out for exercise, to work, socially) differed according to tier level. STUDY DESIGN: Cross-sectional, nationally representative, online survey of 1728 participants living in England (data collection: 26 to 28 October 2020). METHODS: We conducted logistic regression analyses to investigate whether knowledge of restrictions, confidence in knowledge of restrictions, motivation to adhere to restrictions, and self-reported behaviour were associated with personal characteristics and tier. RESULTS: Between 81% (tier 2) and 89% (tier 3) of participants correctly identified which tier they lived in. Knowledge of specific restrictions was variable. 73% were confident that they understood which tier was in place in their local area, whereas 71% were confident they understood the guidance in their local area. Confidence was associated with being older and living in a less deprived area. 73% were motivated to adhere to restrictions in their local area. Motivation was associated with being female and older. People living in tiers with greater restrictions were less likely to report going out to meet people from another household socially; reported rates of going out for exercise and for work did not differ. CONCLUSIONS: Although recognition of local tier level was high, knowledge of specific guidance for tiers was variable. There was some indication that nuanced guidance (e.g. behaviour allowed in some settings but not others) was more poorly understood than guidance which was absolute (i.e. behaviour is either allowed or not allowed).

COVID-19 vaccination acceptability in the UK at the start of the vaccination programme: a nationally representative cross-sectional survey (CoVAccS - wave 2).

OBJECTIVES: Investigate factors associated with the intention to have the COVID-19 vaccination following initiation of the UK national vaccination programme. STUDY DESIGN: An online cross-sectional survey completed by 1500 adults (13th-15th January 2021). METHODS: Linear regression analyses were used to investigate associations between intention to be vaccinated for COVID-19 and sociodemographic factors, previous influenza vaccination, attitudes and beliefs about COVID-19 and COVID-19 vaccination and vaccination in general. Participants' main reasons for likely vaccination (non-)uptake were also solicited. RESULTS: 73.5% of participants (95% CI 71.2%, 75.7%) reported being likely to be vaccinated against COVID-19, 17.3% (95% CI 15.4%, 19.3%) were unsure, and 9.3% (95% CI 7.9%, 10.8%) reported being unlikely to be vaccinated. The full regression model explained 69.8% of the variance in intention. Intention was associated with: having been/intending to be vaccinated for influenza last winter/this winter; stronger beliefs about social acceptability of a COVID-19 vaccine; the perceived need for vaccination; adequacy of information about the vaccine; and weaker beliefs that the vaccine is unsafe. Beliefs that only those at serious risk of illness should be vaccinated and that the vaccines are just a means for manufacturers to make money were negatively associated with vaccination intention. CONCLUSIONS: Most participants reported being likely to get the COVID-19 vaccination. COVID-19 vaccination attitudes and beliefs are a crucial factor underpinning vaccine intention. Continued engagement with the public with a focus on the importance and safety of vaccination is recommended.

Learning about COVID-19 across borders: public health information and adherence among international travellers to the UK.

OBJECTIVE: Public health control measures at borders have long been central to national strategies for the prevention and containment of infectious diseases. Travel was inevitably associated with the rapid global transmission of COVID-19. In the UK, public health authorities tried to reduce the risks of travel-associated spread by providing public health information at ports of entry. This study investigates risk assessment processes, decision-making and adherence to official advice among international travellers, to provide evidence for future policy on the provision of public health information to facilitate safer international travel. STUDY DESIGN: This study is a qualitative study evaluation. METHOD: International air passengers arriving at the London Heathrow Airport on scheduled flights from China and Singapore were approached for interview after consenting to contact in completed surveys. Semi-structured interviews were conducted by telephone, using two topic guides to explore views of official public health information and self-isolation. Interview transcripts were coded and analysed thematically. RESULTS: Participants regarded official advice from Public Health England as adequate at the time, despite observing differences with intervention measures implemented in their countries of departure. Most participants also described adopting precautionary measures, including self-isolation and the use of face coverings that went beyond official advice, but reported adherence to guidance on contacting health authorities was more variable. Adherence to the official guidance was informed by the perceived salience of specific transmission possibilities and containment measures assessed in relation to participants' local social and institutional environments. CONCLUSION: Analysis of study findings demonstrates that international air travellers' responses to public health advice constitute a proactive process of risk assessment and rationalised decision-making to guide preventive action. This process incorporates consideration of the current living situation, trust in information sources, correspondence with cultural logics and willingness to accept potential risk to self and significant others. Our findings concerning international passengers' understanding of, and compliance with, official advice and mitigation measures provide valuable evidence to inform future policy and generate recommendations on the presentation of public health information to facilitate safer international travel. Access to a central source of regularly updated official information would help minimise confusion between different national guidelines. Greater attention to the differentiated information needs of diverse groups in creating future public-facing guidance would help to minimise the uncertainties generated by the receipt of generic information.

The development and validation of the secondary exercise addiction scale.

OBJECTIVES: Exercise addiction can be secondary to eating disorders, or a primary condition in the absence of another disorder. Currently, to determine secondary exercise addiction, two screening tools must be administered. The aim of this study was to validate a novel screening tool able to stratify between primary and secondary exercise addiction, called the secondary exercise addiction scale (SEAS). METHODS: Phase 1 (n = 339) described the statistical reduction of an initial pool of scale items. Phase 2 (n = 382) used a confirmatory factor analysis (CFA) to examine the robustness of the latent structure. Phase 3 (n = 721) determined cut off scores for the eating disorder and exercise addiction sections of the SEAS and determine concurrent reliability with the exercise addiction inventory (EAI) and the SCOFF questionnaires. Phase 4 (n = 45) determined test-retest reliability. RESULTS: Phase 1 extracted two components: exercise addiction and eating disorder symptomology, with 11 items retained. The CFA in Phase 2 showed an acceptable fit to the proposed model (comparative fit index = 0.93, Tucker Lewis Index = 0.91). Phase 3 determined cut off scores of ≥ 28 (specificity = 91.97%), and ≥ 20 (specificity = 96.27%) in the respective exercise addiction and eating disorders sections of the SEAS. The respective sections also correlated well with the EAI (r = 0.70, p = < 0.001) and the SCOFF (r = 0.72, p = < 0.001). Phase 4 showed excellent test-retest reliability (exercise addiction r = 0.95, p = < 0.001, eating disorders r = 0.93, p = < 0.001). CONCLUSION: The SEAS appears to be a valid and reliable tool for measuring primary and secondary exercise addiction. Further studies are warranted to further validate this tool amongst clinical populations. LEVEL OF EVIDENCE: Level III: evidence obtained from cohort or case-control analytic studies.

Reference range for 24-h urine calcium, calcium/creatinine ratio, and correlations with calcium absorption and serum vitamin D metabolites in normal women.

A study of 959 black and white women shows that the normal range for 24-h urine calcium excretion in white women is 30-300 mg and 10-285 mg in black women. Clinical laboratories use a normal range for 24-h urine calcium excretion of 100-300 mg; there is a need for them to update their age- and race-specific ranges. INTRODUCTION: Recommendations for a normal range for 24-h urine calcium vary from a low of 50 mg to a high of 400 mg; most "laboratory normal ranges" based on older literature are incorrect. The objective of this analysis is to define a normal range for young women age 25-45 years and older women age 55-90 years, white and black, for 24-h urine calcium and calcium/creatinine ratio, and to examine the relationship between 24-h urine calcium, calcium absorption, and vitamin D metabolites. METHODS: Data from 3 studies was collected on 959 normal black and white women, ages 25-87 years, for 24-h urine calcium, creatinine, calcium intake, serum 25-hydroxyvitamin D (25OHD),1,25 dihydroxyvitamin D (1,25(OH)2D), and calcium absorption. Urine calcium and creatinine were measured on an auto-analyzer. Calcium absorption was measured by a single isotope method. Serum 25OHD and 1,25(OH)2D were measured by competitive protein binding assay or radioimmunoassay. Because 24-h urine calcium did not fit a normal distribution, non-parametric methods were used to determine the 95% reference interval (RI) and 90% non-parametric confidence intervals (CI) calculated for groups. RESULTS: The 95% reference intervals for 24-h urine calcium for women were as follows: black older 7-225 mg, black younger 8-285 mg; white older 37-275 mg, and white younger 23-287 mg. In older white women, 24-h urine calcium was significantly correlated with serum 1,25(OH)2 D, r = 0.23, p < 0.001, calcium intake r = 0.12, p = 0.001, and calcium absorption r = 0.18, p = 0.003, but not serum 25OHD r = 0.07, p = 0.06. CONCLUSIONS: The normal reference interval for 24-h urine calcium for black women is lower than white women. Twenty-four-hour urine calcium was correlated with serum 1,25(OH)2 D calcium intake and calcium absorption, but not serum 25OHD. This range will be useful clinically for defining hypercalciuria and for following patients on vitamin D and calcium treatment.

Macrophage activation in the lung during the progression of nitrogen mustard induced injury is associated with histone modifications and altered miRNA expression.

Activated macrophages have been implicated in lung injury and fibrosis induced by the cytotoxic alkylating agent, nitrogen mustard (NM). Herein, we determined if macrophage activation is associated with histone modifications and altered miRNA expression. Treatment of rats with NM (0.125 mg/kg, i.t.) resulted in increases in phosphorylation of H2A.X in lung macrophages at 1 d and 3 d post-exposure. This DNA damage response was accompanied by methylation of histone (H) 3 lysine (K) 4 and acetylation of H3K9, marks of transcriptional activation, and methylation of H3K36 and H3K9, marks associated with transcriptional repression. Increases in histone acetyl transferase and histone deacetylase were also observed in macrophages 1 d and 28 d post-NM exposure. PCR array analysis of miRNAs (miR)s involved in inflammation and fibrosis revealed unique and overlapping expression profiles in macrophages isolated 1, 3, 7, and 28 d post-NM. An IPA Core Analysis of predicted mRNA targets of differentially expressed miRNAs identified significant enrichment of Diseases and Functions related to cell cycle arrest, apoptosis, cell movement, cell adhesion, lipid metabolism, and inflammation 1 d and 28 d post NM. miRNA-mRNA interaction network analysis revealed highly connected miRNAs representing key upstream regulators of mRNAs involved in significantly enriched pathways including miR-34c-5p and miR-27a-3p at 1 d post NM and miR-125b-5p, miR-16-5p, miR-30c-5p, miR-19b-3p and miR-148b-3p at 28 d post NM. Collectively, these data show that NM promotes histone remodeling and alterations in miRNA expression linked to lung macrophage responses during inflammatory injury and fibrosis.